Two naturally occurring viral infections of domestic animals are used as models for studying the unusual host-virus interactions that result in slowly evolving diseases. These are (1) scrapie of sheep and goats and (2) Aleutian disease of ranch mink. Scrapie is a degenerative disease of the brain (polioencephalopathy) caused by an unconventional virus (scrapie agent) replicating in central nervous tissue. Aleutian disease, caused by a nondefective parvovirus, is mainly a chronic renal disease mediated by infectious immune complexes that become deposited in the glomeruli. Simple methods of clinical observation, serology, virology, animal inoculation, and anatomic pathology are used to obtain information on the pathogenesis and natural history of each disease. Such information helps characterize each disease as a nosologic entity and provides a better understanding of the way it comes about. In addition, such information on the animal diseases will help determine the relation of slow viral infection to the genesis of chronic disease in man. Included in the project is one such disease, Creutzfeldt-Jakob disease, for whih scrapie is the prototype.